miR-638 Serves as a Biomarker of 5-Fluorouracil Sensitivity to Neoadjuvant Chemotherapy in Breast Cancer

• Published in: Journal of breast cancer Vol. 25; no. 3; pp. 193 - 206
• Main Authors: Wang, Bin, Wang, Kun, Yu, Jian, Hao, Xiao-meng, Liu, Yu-lu, Xing, Ai-Yan
• Format: Journal Article
• Language: English
• Published: Korean Breast Cancer Society 01.06.2022
• Subjects: Original
• ISSN: 1738-6756; 2092-9900
• DOI: 10.4048/jbc.2022.25.e24

PURPOSENeoadjuvant chemotherapy (NAC) is widely used to treat breast cancer (BC). The prediction and evaluation of chemotherapy responses remains a significant challenge. METHODSMicroRNAs (miRNAs) play a crucial role in cancer drug resistance. We used a miRNA microarray and identified that miR-638 is downregulated in chemoresistant cases. However, the exact role of miR-638 and the underlying mechanisms of chemoresistance remain unclear. Using real-time quantitative reverse transcription polymerase chain reaction, we found significant downregulation of miR-638 in chemoresistant patients compared with chemosensitive patients. To explore the function of miR-638, we overexpressed and inhibited miR-638 expression in MDA-MB-231 and MCF-7 cells by transfecting them with miR-638 mimics and miR-638 inhibitor, respectively. Cell proliferation and apoptosis were measured using MTS and flow cytometry, respectively. A minimal patient-derived xenograft (MiniPDX™) model was established to evaluate the chemosensitivity to different drugs. RESULTSThe results showed that cell proliferation decreased and cell apoptosis increased in cells transfected with the miR-638 mimic, and cell proliferation and apoptosis were reversed with transfection of miR-638 inhibitor compared with the control group. Among patients who received 5-fluorouracil (5-FU), miR-638 expression levels were lower in the chemoresistant group than in the chemosensitive group. The MiniPDX™ model showed that MDA-MB-231 cells overexpressing miR-638 were more susceptible to 5-FU treatment in vivo. CONCLUSIONWe provided evidence of acquired resistance to 5-FU caused by miR-638 deficiency. Alterations in miR-638 may be used with 5-FU chemotherapy during NAC for BC.